Process for the preparation of 17-oxo-steroids from 17a-hydroxy-20-oxo-steroids

ABSTRACT

Process for the preparation of 17-oxo-steroids which comprises oxidizing 17 Alpha -hydroxy-20-oxo-steroids by means of oneelectron transfer oxidizing agents.

United States Patent [191 Turnbull Feb. 27, E973 PROCESS FOR THEPREPARATION OF l7-OXO-STEROIDS FROM 17a- HYDROXY-ZO-OXO-STEROIDSInventor: John Peter Turnbull,

England London,

Assignee: Glaxo Laboratories Limited, Middlesex, England Filed: Dec. 21,1970 Appl. No.: 100,402

US. Cl. ..260/397.3, 260/397.4, 260/397.45 Int. Cl ..C07c 169/22 [58]Field of Search ..260/397.3, 397.5

Primary ExaminerElbert L. Roberts Attorney-Bacon & Thomas [57] ABSTRACT6 Claims, N0 Drawings PROCESS FOR THE PREPARATION OF l7-OXO- STEROIDSFROM l7a-HYDROXY-20-OXO- STEROIDS This invention relates to a processfor the production of 17-oxo steroids from l7 -hydroxy-20-oxosteroids.

Steroids having a l7a-hydroxy group and a 20-oxo group are of frequentoccurrence in. steroid synthesis and many have valuable physiologicalproperties esperoids by reaction with organometallic reagents and it ispossible to convert l7a-hydroxy-20-oxo steroids into l7-oxo steroids byoxidative ketol cleavage using such reagents as chromium trioxide, orlead tetraacetate. However, these reagents are generally non-selectivein their attack when other oxidizable groupings are present in thesteroid and have generally proved unsuitable.

We have now found that l7a-hydroxy-20-oxo steroids and derivativesthereof possessing a grouping which is convertible to a 20-oxo-group,can be oxidized particularly smoothly and selectively to l7-oxo-steroidsby l-electron transfer oxidizing agents.

The term one-electron transfer oxidizing agent means any oxidizingreagent which effects oxidation by removal of a single electron from thesubstrate to be oxidized and includes, in particular, ceric salts,especially readily water soluble ceric salts such as ceric ammoniumsalts, e.g. ceric ammonium nitrate or ceric perchlorate, argentic salts,for example argentic picolinate, argentic oxide and vanadates such as analkali metal or ammonium vanadate e.g. sodium or potassium vanadate.Other one-electron transfer oxidizing agents of about the same order ofoxidation potential as ceric and argentic salts or vanadates or greatermay also advantageously be used.

The ceric oxidation is preferably effected under acidic conditions e.g.in an aqueous solution of an inorganic or organic acid, for example analiphatic acid such as acetic or propionic acid or nitric or sulphuricacid. The reactants may be partially or wholly in solution. An organicsolvent for the steroid is preferably present, e.g. a cyclic ethersolvent such as tetrahydrofuran or dioxan, a substituted amide solventsuch as dimethylformamide or dimethylacetamide or a nitrile solvent suchas acetonitrile but an aliphatic acid used to acidify the medium mayalso serve as solvent. An alcoholsuch as methanol, ethanol, isopropanolor t-butanol, or a ketone such as acetone or methyl ethyl ketone may beused as solvent but will be slowly oxidized with consequent waste ofreagent. It will be noted that the ceric salt itself will normallyrender the medium acidic; added acid may, however, be beneficial. Theargentic oxidation may advantageously be effected under acidic or basicconditions. The use of a vanadate as oxidizing agent generally requiresa strongly acidic solution, in particular, to provide sufficientsolubility for the reactants.

The ceric oxidizing agents, in particular, react more rapidly thanpreviously proposed oxidizing reagents as well as being more selectiveand have the added advantages of easy working up, high recovery levelsof reagent and economical use of reagent.

Although ceric salts in general may be used for the process of theinvention, we particularly prefer to use ceric ammonium nitrate whileceric sulphate is less preferred due to possible complex formation. Astoichiometric quantity or, more preferably a slight excess, ofoxidizing agent is preferred, for example 2 to 4 moles (l to 2equivalents), e.g. about 2.5 moles. Disadvantages may result from theuse of a substantial excess of oxidizing agent, for example oxidation atsome point other than the l7-position of the steroids present in thereaction mixture. The risk of such oxidation will, of course, dependupon the exact nature of the steroids concerned. However, the process ofthis invention provides a generally more facile and specific oxidativecleavage of the 17,20-bond of a l7a-hydroxy-20-oxosteroid thanpreviously proposed methods.

The reaction time may be of the order of hours although a few minutes isgenerally sufficient and in some cases less than one minute may beenough. The course of the reaction may be observed by color changeswhich take place in the solution in which the oxidation is effected. Inceric oxidation a red color is frequently initially formed when theoxidizing agent is added and this color generally fades to a pale yellowor lighter color. These color changes should not however, be consideredas giving more than an indication of the progress of the desiredoxidation.

The reaction may conveniently be effected at ambient temperaturealthough higher or lower temperatures may also be used. As indicatedabove, l7-oxo steroids are of especial value as intermediates in theproduction of l7B-hydroxy steroids having a 17ahydrocarbon substituent,for example a l7a-ethynyl group, but many l7-oxo steroids arephysiologically active themselves. The method according to the presentinvention thus affords a useful means whereby a wide range of l7-oxosteroids and their derivatives can be prepared from relatively commonsteroid sources.

By the term steroid as used herein we mean compounds which have thecyclopentanoperhydrophenanthrene structure and which may carry varioussubstituents on the ring structure, for example, alkyl groups, e.g.methyl groups, hydroxy groups, protected hydroxy groups, keto groups,protected keto groups or halogen atoms; a hydroxyl group adjacent to anoxo group or a further hydroxyl group is preferably protected, e.g. byesterification or etherification.

Position 6- may be unsubstituted or substituted, for example, by analkyl group, in particular a methyl group, or a halogen atom,particularly a fluorine or chlorine atom.

The 9- position may, for example, carry a halogen atom, e.g. fluorine,chlorine or bromine, preferably in the a-configuration.

The 10- and l3-positions may be unsubstituted but will more commonlycarry an alkyl group such as the methyl group present in the androstanesand pregnanes, which alkyl group may be substituted, e.g. by a hydroxygroup, as in IO-hydroxymethyl steroids. The l0-position may also carry ahydroxy group.

The 11- and 12- positions may be unsubstituted or may be substituted,for example, by hydroxy or keto groups or halogen atoms. Hydroxyl groupsat these positions may be protected e.g. by esterification oretherification and x0 groups may also be protected, for example byreduction to hydroxy] followed by protection or by conversion to aketal. Any halogen atoms which are present are preferably fluorine,chlorine or bromine atoms.

The l6-position may be unsubstituted or may for example, carry an alkylor alkylene substituent, e.g. a methyl or ethyl group or an exocyclicmethylene group.

The l7B-position of the l7a-hydroxy-steroid carries a -CO group or agroup convertible thereto, joined to a further grouping. Thus, forexample, the l7B-position may carry a carboxyl or carboxylic ester groupe.g. an alkoxy-carbonyl group having l-6 carbon atoms in the alkylportion; or more preferably, an acetyl group, which may carrysubstituents for example a hydroxy group, an acyloxy group e.g. analiphatic acyloxy group preferably having l-6 carbon atoms, anaraliphatic acyloxy group, preferably having l-6 carbon atoms in thealiphatic portionor an aryl acyloxy group, the aryl and araliphaticacyloxy groups preferably being monocyclic, a hydrocarbon sulphonyloxygroup e.g. a methane or p-toluenesulphonyloxy group, a halogen atom,e.g. fluorine, chlorine or bromine atom, or an alkyl group, preferablyhaving 1-5 carbon atoms. The steroid may thus be al7a-hydroxy-20-oxo-pregnane carrying at the 2l-position a hydroxy oracetoxy group, or more preferably, being unsubstituted at the2l-position.

In the case of steroids possessing at the 20-position a groupconvertible to an 0x0 group this group may for example, be a ketal e.g.an acyclic ketal formed with two molecules of an alcohol e.g. analiphatic alcohol having l-5 carbon atoms, or a cyclic ketal formed witha diol e.g. ethylene glycol, propane-1,2-diol or butane- 2,3-diol. Othergroupings convertible to a 20-oxo group include imines such as oxime'and alkoxime, e.g. methoxime, groups. Such derivatives are oxidizedaccording to the process of the present invention in the same way as the20-oxo-steroid without significantly affecting the formation of thedesired l7-oxo steroid.

The process according to the invention may be used for the oxidation ofl7a-hydroxy-20-oxo-steroids possessing one or more double bonds, forexample in the l,2-; 2,3-; 3,4-; 4,5-; 5,6-; 6,7-; 9,1l-; ll,l2- or15,16- positions.

The 3-position may, in general, bear an oxygen substituent in the form,for example, of a keto group or a hydroxy group, which may berespectively in the form of a ketal derivative, or an acyl derivativee.g. an aliphatic acyloxy group preferably having -l-6 carbon atoms,e.g. an acetoxy group, an araliphatic acyloxy group, preferably havingl-6 carbon atoms in the aliphatic portion or an aryl acyloxy group, e.g.a benzoyloxy group, the aryl and araliphatic acyloxy groups preferablybeing monocyclic; a hydrocarbon sulphonyloxy group, e.g. a methane orptoluenesulphonyloxy group; or an ether group, e.g. an alkoxy oraralkoxy group having l-5 carbon atoms in the aliphatic portion or anaryloxy group, the aryloxy or aralkoxy groups preferably beingmonocyclic. Where the A-ring is aromatic and an oxygen substituent, e.g.

an acyloxy or ether group, is present in the 3-position, reaction maytake place at the 9- and l lpositions and, for example, ceric salts inthe presence of nitrate ions yield 1 lB-nitro-oxy-9-hydroxy steroids.

The stereochemistry of the junction between the A and B rings alsoappears to have little effect on the course of the present reactionand-compounds having either cis-or trans- AB ring junctions may beoxidized. The S-position in such cases usually carries a hydrogen atom.

As indicated above, the process according to the invention is especiallyuseful in converting l7a-hydroxy- 20-oxo-pregnanes which are already inuse, and are therefore available at an economical nrice, intocorresponding l7-oxo-steroids which can serve as intermediates in thepreparation of l7a-hydrocarbyl-l7fihydroxy steroids by reaction withorganometallic reagents. Thus, for example in our British Pat. No.1,202,521, we have described both 1 la-hydroxy-oestr- 4-ene-3,l7-dioneand l la,17a-dihydroxy-l9-norpregn-4-ene-3,20-dione as intermediates inthe preparation of ll B-chloro-oestr-4-ene-3,l7-dione and l lB-chlorol7a-hydroxyl 9-norpregn-4-ene-3,20- dione respectively, which areintermediates in the preparation of l lB-chloro-l7a-ethynyl-l7B-hydroxyoestr-4-ene-3-one and l7a-acetoxy-6,llB-dichloro- 1 9- norpregn-4,6-dien-3,20-dione respectively both ofwhich are highly active progestagens; the present process enables 1 la-1 7a-dihydroxy-l 9-norpregn-4- ene-3,20-dione to serve as a commonintermediate in the preparation of both progestagens with consequenteconomic advantages.

The following Examples are given by way of illustration only: alltemperatures are in C:

Melting points were determined in open capillaries and are corrected.Optical rotations are for chloroform solutions except where statedotherwise. Plates for thin-layer chromatography were coated with MerckKieselgel PF and were visualized by spraying with 2N sulphuric acid andbaking at ca.

In all the Examples l-l5 and 17-24 described below the reaction wascarried out in essentially the same way. A stirred solution orsuspension of steroid in a suitable water-miscible solvent was treatedat ambient temperature with an appropriate amount (l-l .5 equivs.) ofmolar aqueous ceric ammoniumnitrate (546 g. per liter). Completion ofeach reaction was indicated by disappearance of the initially-formed redcoloration, and confirmed by thin-layer chromatography. The weight ofstarting material, solvent, volumes of solvent and reagent employed, andreaction time for each Example are tabulated in Tables IA and "A.

Each product was isolated by one of the following methods:

Method A When the reaction was complete, the reaction mixture was slowlydiluted with water (ca. 5 X the volume of the reaction mixture). Afterca. 1 hr. the crystalline product was filtered off, washed with water,then light petroleum (b.p. 40/60) and dried. The yield, m.p. and [01],,of each product isolated by Method A are listed in Table IB.

Method B When the reaction was complete the reaction mixture was pouredinto water and the product was extracted into ethyl acetate. The extractwas washed with dilute aqueous alkali, then with water, and was thenevaporated in vacuo. After filtration through a little magnesiumsilicate in methylene chloride or chloroform, the residue wascrystallized from a suitable solvent. The yield, crystallizing solvent,m.p. and [01],, for each product isolated by method B are listed inTable 11B.

COMPOUNDS PREPARED FOLLOWING METHOD TABLE IA Starting Vol- Vol. ofReaction Example material solvent of solvent reagent time (mg.) (m1.)(ml) (min) acetic 1 180 acid 2.5 1.3 15

acetic 7a 3470 50 25 20 acid 7b 3470 ethanol 50 30 100 acetic 8a 195 31.1 1

acid 8b 195 Dioxan 3 1.2 2

acetic 9a 217 3 1.2 3

acid 9b 217 Dioxan 3 1.2

acetic 14 230 3 1.4 10 acid acetic 82 2 1.0

acid acetic 1712 392 5 2.5 10

acid acetic 18a 376 10 2.0 1

acid acetic 19 374 10 2.2 30

acid acetic 21 1000 15 7.0

acid

acetic 24 64 2 0.5 10

acid

COMPOUNDS PREPARED FOLLOWING METHOD TABLE IB Product Yield m.p. [01)Example 35 216-219" +308 (0.1.01) 1 70 168-471 +193 (c,1.00) 7a 67161-168 +189 (c,l.28) 7b 80 148-15l +97 (0,0.51) 8a 78 151-153+105(c,0.50) 8b 85 153.5-155 +103 (0.0.50) 9a 79 154-19565: +104(0,0.50) 9b 78 (dec) 14 40 166-168 +189 (c,0.50) 15 40 240-242" +l04(0,0.50) 17b 55 270-275: +102 (0.0.50) 1'8; 70 182-185 COMPOUNDSPREPARED FOLLOWING METHOD TABLEIIA Starting Vol. Vol. of ReactionExample material Solvent of solvent reagent time (mg.) (ml.) (ml.) (min)acetic acid acetic acid acetic acid acetic acid acetic acid acetic acidacetic acid acetic acid acetic acid acetic acid acetic acid acetic acidacetic acid acetic acid COMPOUNDS PREPARED FOLLOWING METHOD TABLE 11BProduct Ex: Crystallization Solvent m.p. [01],,

Yield +187 2 Cyclohexanelchloroform 40 168.5- (0,095)

+160 3 Cyclohexanewhloroform 67 176.5- (c,1.02)

178 4 Aq. methanol 65 169- +140 (0,0.50)

171 5 Ethyl acetate 45 206- 208 6 Cyclohexane/methylene 49 187- +250(c,0.50) chloride 189 10 Cyclohexane/methylene 68 183- +102 (0,0.50)chloride 188 l1 Cyclohexane/methylene 69 194- +222 (0,0.58 clloride 198in acetone) 1 (c.0.59 12 Aq. acetone 30 187 +103 in acetone) 13Cyclohexane/methylene l chloride 61 153- +l54 (0.1.00)

154 17a Aq. methanol 66 221- 98 (c,0.80)

227 18b Aq. methanol 30 +105(c,0.50)

20 Methanol 35 151- +l98 (c,0.50)

153 22 Acetone/light petroleum 233- (b.p. 40-60) 46 235 9 (0.0.95 (dec)in DMSO) 233- 23 Acetone 33 238 (dec) EXAMPLE 1 Androst-4-ene-3,l1,17-trione:

From l711,21-dihydroxy-pregn-4-ene-3 ,1 1,20-trione the title compoundwas obtained following isolation by Method A.

EXAMPLE 2 19-l-lydroxyandrost-4-ene-3 ,17-dione:

From l7a,19-dihydroxypregn-4-ene-3,20-dione, the title compound wasobtained following isolation by Method B.

EXAMPLE 3 a-Androstane-3,1 1,17- trione:

From l7a-hydroxy-5a-pregnane-3.l 1,20-trione, the title compound wasobtained following isolation by Method B.

EXAMPLE 4 Oestr-4-ene-3,17-dione From l7a-hydroxy- 1 9-norpregn-4-ene-3,20-dione the title compound was obtained following isolation by MethodB.

EXAMPLE 5 l 1a-l-lydroxyoestr-4-ene-3,l 7-dione:

From l1a,17a-dihydroxy-l9-norpregn-4-ene-3,20- dione the title compoundwas obtained following isolation by Method B.

EXAMPLE 6 l 1B-Chloro-oestr-4-ene-3,17-dione:

From 1 lfl-chloro-17a-hydroxy-l9-norpregn-4-ene- 3,20-dione, the titlecompound was obtained following isolation by Method B.

EXAMPLE 7 Androst-4-ene-3,17-dione:

From l7a,2 l -dihydroxy-pregn-4-ene-3 ,20-dione, the title compound wasobtained following isolation by Method B. In separate preparations,acetic acid (Example 7a) and ethanol (Example 7b) were used as reactionsolvent. The product in 7b contained ca. 2 percent of starting material.

EXAMPLE 8 3B-Acetoxy-5a-androstane1 1,17-dione:

From SIS-acetoxy-l 7a-hydroxy-5a-pregnane-l 1,20- dione, the titlecompound was obtained following isolation by Method A. In separatepreparations, acetic acid (Example 8a) and dioxan (Example 8b) were usedas reaction solvent. The material obtained in 8a contained ca. 2 percentof starting material.

EXAMPLE 9 3B-Acetoxy-5a-androstane-l 1,17-dione:

From 3fi-acetoxy-20,20-ethylenedioxy-l7a-hydroxy-Sa-pregnan-l l-one, thetitle compound was obtained following isolation by Method A. In separatepreparations, acetic acid (Example 9a) and dioxan (Example 9b) were usedas reaction solvent.

EXAMPLE 10 3B-Hydroxy-l 6fl-methyl-5a-androstane- 1 1,17-dione:

From 318,1 7a-hydroxy-l 6B-methyl-5a-pregnanel 1,20-dione the titlecompound was obtained following isolation by Method B.

EXAMPLE 1 l Androsta-l ,4-diene-3,l l, l 7-trione:

From 17a,21-dihydroxypregna-1,4-diene-3 ,1 1,20- trione, the titlecompound was obtained following isolation by Method B.

EXAMPLE l2 1 lB-Hydroxyandrosta-l ,4-diene-3 ,1 7-dione:

From 1 15,17a,2l-trihydroxypregna-1,4-diene-3,20- dione, the titlecompound was obtained following isolation by Method B.

EXAMPLE l3 5a-Androst-9( 1 1 )-ene-3, 1 7-dione:

From l7a-hydroxy-5a-pregn-9( l 1 )-ene-3,20-dione, the title compoundwas obtained following isolation by Method B, except that purificationof the product was by chromatography over alumina (Spence, Grade H) inmethylene chloride in place of filtration through magnesium silicate.

EXAMPLE 14 3B-Acetoxy-9a,l lB-dichloro-l6B-methyl-5a-androstanl 7-one:

From 3B-acetoxy-9a,1 1 B-dichloro-l 7a-hydroxy-l 6B -methylSa-pregnan-ZO-one, the title compound was obtained following isolationby Method A. A recrystallized sample (aq. methanol) had m.p. l98-204(dec) [a] +74 (c,0.60).

EXAMPLE 15 Androst-4-ene-3 l 7-dione:

From l7B-carboxy- 1 7a-hydroxy-androst-4-en-3- one, the title compoundwas prepared following isolation by Method A.

EXAMPLE 16 17a-l-lydroxy-l 9-nor-5B-pregnane-3,20-dione:

l7a-Hydroxy-l 9-norpregn-4-ene-3,20-dione (320 mg) in ethyl acetate (30ml.) was hydrogenated over 10 percent palladium-on-charcoal (320 mg.) atambient temperature and pressure until uptake ceased.

Removal of the catalyst by filtration and concentration of the filtrategave the title compound as needles mg; 57 percent) m.p. 226-229; [01],,17.5 (c,0.65).

EXAMPLE 17 EXAMPLE l8 9a-Fluoro-l lB-hydroxy-16B-methyl-androsta-l ,4-diene-3,17-dione:

a. From 1 13,17a-dihydroxy-9a-fluoro-1 6B-methylpregna-l,4-diene-3,20-dione, the title compound was obtained following isolationby Method A.

b. From 9a-fluoro-l6B-methyl-l 13,1 7a,2ltrihydroxypregna-l,4-diene-3,20-dione, the title compound was obtained following isolationby Method B.

EXAMPLE l9 9a-Fluoro-l fl-methylandrosta-l ,4-diene-3 ,1 1,17- trione:

From 9a-fluoro-17ahydroxy-l6B-methylpregnal,4-diene-3,l1,20-trione, thetitle compound was obtained following isolation by Method A. Arecrystallized sample (aq. methanol) had m.p. l88.5-l90; [a] 213(c,0.50).

EXAMPLE 20 6,1 1B-Dichloro-oestra-4,6-diene-3,l7-dione:

From 6,1 lB-dichloro-l 7a-hydroxyl 9-norpregna- 4,6-diene-3,20-dione,the title compound was obtained, following isolation by Method B.

EXAMPLE 21 Androsta-l ,4,9( l l )-triene-3 ,17-dione: v

From l7a-hydroxypregna-l ,4,9(l 1)-triene-3 ,20-

LII

dione the title compound was obtained following isolation by method A. gp

EXAMPLE 22 9a-Fluoro-l lB-hydroxyl 6-methylene-androstal ,4- diene-3, l7-dione:

From 9a-fluoro-l 113,1 7a-dihydroxy- 16-methylenepregna-l,4-diene-3,20-dione, the title compound was obtained,following isolation by Method B, including preparative thin-layerchomatography.

EXAMPLE 23 9a-Fluoro-l lB-hydroxyl 6-methylene-androsta-l ,4-diene-3,l7-dione:

From 9a-fluoro-l lB,17a,2l-trihydroxy-l6-methylene-pregnal,4-diene-3,20-dione, the title compound was obtainedfollowing isolation by Method B, including preparative thin-layerchromatography.

EXAMPLE 24 Sfl-Ostrarie-S, 1 7-dione:

From l7a-hydroxy-l 9-nor-5B-pregnane-3,20-dione ""1 the title compoundwas obtained following isolation by 2, Method A.

EXAMPLE 25 3BAcetoxy-Sa-androstane-l 1,17-dione using various (b.p.40/60)-acetone (3:1 as solvent. Results are tabulated below.

Starting Material Solvent 17-Ketone (Rp- 0.4) (R; 0.5) Acetone 30 60Tert-butanol 20 Tetrahydrofuran 45 40 Dimethylformamide 20 Methanol 1575 Acetonitrile 5 EXAMPLE Z6 Oestr-4-ene-3,l 7-dione using oxidantsother than ceric ammonium nitrate:

a. A solution of ca 0.5 molar ceric perchlorate in N aqueous perchloricacid was prepared by stirring ceric sulphate (10 g.) in N aqueousperchloric acid (30 ml.) with a solution of barium perchloratetrihydrate (20 g.; ca 1.1 equiv.) in N aqueous perchloric acid (10 ml.).After 18 hr. the precipitate was removed by centrifugation and thesupernatant ceric perchlorate solution was used without furtherprocessing.

17a-l-lydroxy-l 9-norpregn-4-ene-3,20-dione mg.) in acetic acid (3 ml.)was treated with ca 0.5 molar aqueous ceric perchlorate (as describedabove) in 1 ml. portions until the yellow color was not rapidlydischarged (4 ml. required). Thin-layer chromatographic analysis of themixture (as described in Example 25) indicated formation of the titlecompound (R,- -0.45 in ca. 85 percent amount.

b. Ammonium vanadate (468 mg.) was added with cooling to a solution of98 percent sulphuric acid (1.0 ml.) in acetic acid (5 ml.) and water(5ml.). To the resultant red/brown slurry was added a solution of17ahydroxy-l9-norpregn-4-ene-3,20-dione- (317 mg.) in acetic acid. After3 hr., the red-brown solid had dissolved and the solution was green/blueindicating complete consumption of the oxidant. ThinJayerchromatographic analysis of the product (as described in Example 25 butusing chloroform (2 runs) in place of light petroleum-acetone) indicatedformation of the title compound (R -0.55) in ca. 65 percent amount, with20 percent of starting material unchanged (R,--0.25.

0. Reaction (b) above was repeated except for the use of 70 percentnitric acid (2.0 ml.) in place of 98 percent sulphuric acid. Thin-layerchromatographic analysis of the product after 3 hr. (as in (b) above)indicated formation of the title compound (R -0.55) in ca. 70 percentamount with only a trace of unreacted starting material.

We claim:

1. A process for the preparation of a 17-oxo steroid which comprisesoxidizing a l7a-hydroxy steroid having at the 20-position an oxo-,ketal, or imino group by means of a one-electron transfer oxidizingagent selected from the group consisting of a ceric salt, an argenticsalt, argentic oxide and a vanadate.

2. The process as claimed in claim 1 wherein the oneelectron transferoxidizing agent is ceric ammonium nitrate or ceric perchlorate.

3. The process as claimed in claim 1 wherein the oxidation is effectedin the presence of an organic solvent for the steroid the organicsolvent being a cyclic ether,

a substituted amide, a nitrile or an aliphatic acid.

6. The process as claimed in claim I whcrein the steroid startingmaterial is l l ,l7a-dihydroxy-l9-norpregn-4-ene-3,20 dione or IlB-chl0ro-l7a-hydroxyl9-norpregn-4-cne-3 ,20-dione.

2. The process as claimed in claim 1 wherein the one-electron transferoxidizing agent is ceric ammonium nitrate or ceric perchlorate.
 3. Theprocess as claimed in claim 1 wherein the oxidation is effected in thepresence of an organic solvent for the steroid the organic solvent beinga cyclic ether, a substituted amide, a nitrile or an aliphatic acid. 4.The process as claimed in claim 1 wherein from 2 to 4 moles of the saidoxidizing agent per mole of steroid starting material are used.
 5. Theprocess as claimed in claim 1 wherein the steroid starting material is apregnane in which the 20-position carries a ketal or imine group.
 6. Theprocess as claimed in claim 1 wherein the steroid starting material is11 Alpha ,17 Alpha -dihydroxy-19-norpregn-4-ene-3,20 dione or 11 Beta-chloro-17 Alpha -hydroxy-19-norpregn-4-ene-3,20-dione.